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GPs warned over link between glucose-lowering drugs and heart failure

GPs should consider the potential risk of heart failure when prescribing glucose-lowering treatment, researchers have claimed, after finding drugs used to control blood glucose in patients with or at risk of diabetes are associated with an increase in heart failure incidence.

The researchers’ analysis of 14 randomised controlled trials in over 95,000 patients found a 14% relative increase in incidence of heart failure across all the different types of glucose-lowering interventions tested.

The risk increase appeared to be limited to certain drugs. For thiazolidinediones – including pioglitazone as well as rosiglitazone, which is now no longer marketed in Europe – there was a 42% increase in relative risk of heart failure, while dipeptidyl peptidase-4 (DPP-4) inhibitors were linked to a 25% increased risk overall.

On the other hand, no increase in heart failure was seen with insulin glargine, target-based glycaemic control regimens or weight loss interventions, while glucose-lowering treatments overall were linked to a reduction in heart attacks.

The team concluded: ‘In summary, glucose-lowering by various drugs or strategies might increase the risk of heart failure compared with standard care in patients with or at risk for type 2 diabetes. The magnitude of this risk seems to be driven by specific drug classes and correlated with other trial characteristics, including weight gain and trial duration.

‘Conversely, glucose lowering by various drugs or strategies modestly decreased the risk of myocardial infarction.

‘Clinicians should consider the trade-off between ischaemic and haemodynamic cardiovascular events when choosing between different drugs or strategies for lowering blood glucose.’

Lancet Diabetes Endocrinol 2015; available online 17 March

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Readers' comments (5)

  • Vinci Ho

    Not is all about weight gain as a risk of heart failure .The conclusion states' Meta-regression analysis showed that for every 1·0 kg of weight gain associated with glucose-lowering drugs or strategies, there was a 7·1% (95% CI 1·0–13·6) relative increase in the risk of heart failure compared with standard care (p=0·022).'
    A professor in endocrinologist told me his latest triple therapy before insulin in type2 DM is Metformin + GLP-1 receptor agonist(injectable) + SGLT2 inhibitor (gliflozin). Because they all help to lose weight .

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  • Vinci Ho

    It is all about.....

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  • That is a bit over hyped outcome
    4% risk of heart failure
    Relative increase in risk is 1% to 30% mean of 14%

    so risk of heart failure on drugs may be :
    4.1% or may be even only 4.01%

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  • They obviously haven't read the Alogliptin DPP 4i Examine study and it's extended outcome analysis which has proven evidence to show no increased incidence of HF even in ACS patients that have just had an event after 2 years

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  • Samuel Lewis

    It never ceases to amaze me how many doctors and NHS managers are prepared to prescribe expensive new drugs without a shred of evidence of outcomes benefit . Have they not learned from the Rosiglitazone debacle ?

    for example, the 'Examine' study quoted above concluded that "Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo." No outcomes benefits were demonstrated.

    So that means we should prefer placebos all round, surely ??

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